A PROCESS FOR THE PREPARATION OF VICINAL DIOLS FROM ARYL HALIDE AND OLEFIN USING REUSABLE MULTIFUNCTIONAL CATALYST

Abstract

A process for the preparation of a chiral vicinal diol from aryl halide and olefin using a reusable multifunctional catalyst by two different transition metals essentially one is palladium and another one is selected from the group consisting of ruthenium, osmium, tungsten, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper and molybdenum, said process comprising reacting aryl halide and olefin using the said catalyst by Heck coupling and asymmetric dihydroxylation in the presence of an oxidant and a cinchona alkaloid compound in a solvent selected from the group consisting of water, acetone, acetonitrile and t-butanol, at a temperature in the range of -20 to 200°C for a period ranging from 0.5 to 48 hours and obtaining the desired chiral vicinal diol.

Full Text

The present invention relates to a process for the preparation of vicinal diols from aryl
halide and olefin using reusable multifunctional catalyst. More particularly the present
invention relates to a process for the preparation vicinal diols from aryl halide and olefin by
asymmetric dihydroxylation of olefins in presence of cinchona alkaloid compounds
employing reusable multifunctional catalysts as heterogeneous catalyst.
Heterogeneous multifunctional catalyst used in the above process has been prepared by a
process as claimed and disclosed in our co-pending application no.1199/Del/2001.
The multifunctional catalyst has been prepared by a procedure as claimed and disclosed in
our co-pending application no.1199/Del/2001.
Products obtained by the dihydroxylation of olefins in presence of cinchona alkaloid
compounds are important intermediates for the preparation of drugs and Pharmaceuticals.
For example the products of cinnamic acid esters are intermediates for taxol side chain. An
anticancer drug, diltiazem, calcium antagonist and chloramphenicol can also be derived
from the diols obtained through this method.
There are serious disadvantages in performing the catalytic AD reaction with homogeneous
system in the manufactue of vicinal diols due to presence of toxic remnants of osmium in
products and high cost of osmium tetroxide or potassium osmate dehydrate.
US patent US 4,871,855 and 5,260,421 disclsoe homogeneous asymmetric dihydroxylation
of olefins by osmium tetroxide and cinchona alkaloids. The inherent disadvantages in this
process are cumbersome procedure for the recovery of the osmium catalyst from the
reaction mixture, generation of toxic waste and possibility of presence of toxic osmium in
traces in the product.
US Patent US 5,516,929 discloses heterogeneous asymmetric dihydroxylation of olefins by
osmium tetroxide and polymer-bound cinchona alkaloids. The drawbacks of this process
are the difficulty faced in quantitative recovery of toxic osmium catalyst, lower
enantioselectivity and reduction in activity and enantioselectivity in each and every recycle
experiments.
US patent US 5,968,867 discloses heterogeneous asymmetric dihydroxylation of olefins by
osmium tetroxide and silica gen supported bis-cinchona alkaloid derivatives. The
drawbacks are difficulty in quantitative recovery of toxic osmium catalyst and reduction in activity and enantioselectivity in each and every recycle experiments.
European patent EP 940,170 A2 discloses catalytic asymmetric dihydroxylation of alkenes using a polymer-supported osmium catalyst. The drawbacks are that higher amount of catalyst (5 mol%), longer reaction time and use of expensive polymer as a support are required.
Reference may be made to a publication J. Am. Chem. Soc. 2001, 123, 1365 wherein asymmetric dihydroxylation of olefins is done by osmium tetroxide and a biomimetic flavin in presence of cinchona alkaloids using H2O2 as oxidant under homogeneous conditions. The inherent disadvantages are difficulty in the recovery of osmium tetroxide and usage of unstable flavin.
The main object of the invention is to provide reusable multifunctional catalysts useful for the synthesis of chiral vicinal diols.
Another object of the invention is to prepare reusable multifunctional catalysts having transition metal elements such as palladium, osmium and tugsten deposited in a support having interstitial anions such as chloride, nitrate, carbonate, sulfate or calcined material.
Another object of the invention is to prepare reusable multifunctional catalysts on a single matrix of the support to perform multi-component reaction in a single pot.
It is another object of the invention to provide a novel and ecofriendly process for synthesis of chiral diols from aryl halides and olefins in a single pot.
It is another object of the invention to provide a process for the synthesis of chiral diols dispensing with the use of soluble and toxic; osmium tetraoxide or potassium osmate dihydrate.
It is another object of the invention to provide a multifunctional catalysts are prepared and used as heterogeneous catalysts for synthesis of chiral diols which precludes the presence of osmium in traces with product.
It is another object of the invention to provide a process for the synthesis of chiral vicinal diols where enantioselectivity and the yields are good and work-up procedure simple.
It is another object of the invention to provide a process for the synthesis of chiral vicinal diols which is economical and environmentally safe without any disposal problem.
By employing the heterogeneous catalytic system, the cost naturally comes down due to easy recovery of the catalyst and very insignificant loss of osmium tetroxide, when compared with homogenous system. The products thus obtained using heterogeneous catalyst system are also benign since the presence of osmium in minor impurities in the dihydroxylated products is also precluded.
The present invention provides multifunctional catalysts consisting of palladium, osmium and tungsten species in their composition in its homogeneous or heterogeneous form through ion exchange or anchoring for the preparation of vicinal diols which are important intermediates for drugs and Pharmaceuticals.
Accordingly, the present invention relates to a process for the preparation of vicinal diol from aryl halide and olefin using a reusable multifunctional catalyst having formula S-M, wherein S is a support selected from the group consisting of layered double hydroxide, resin, silica, clay, alumina and S'-NR3X wherein S' is a unmodified support selected from resin and silica, R is an alkyl group selected from the group consisting of methyl, ethyl, propyl and butyl, X is selected from the group consisting of Cl, Br, I, F, OH and OAc; M is an active metal species comprising two different transition metals essentially one is palladium and another one is selected from the group consisting of ruthenium, osmium, tungsten, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper and molybdenum, said process comprising reacting aryl halide and olefin using the said catalyst by Heck coupling and asymmetric dihydroxylation in the presence of an oxidant and a cinchona alkaloid compound in a solvent selected from the group consisting of water, acetone, acetonitrile and t-butanol, at a temperature in the range of -20 to 200°C for a period ranging from 0.5 to 48 hours and obtaining the desired chiral vicinal diol. In one embodiment of the invention, the quantity of multifunctional catalyst used in the reaction is in the range of 0.01 to 10 mol% of active species with respect to the substrate. In one embodiment of the invention, the multifunctional catalyst used is recovered by filtration and is reused for several cycles with consistent activity.
In one embodiment of the invention, the oxidant used is selected from the group consisting of N-methyl morpholine N-oxide (NMO), trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide, potassium ferricyanide, sodium periodate and molecular oxygen. In one embodiment of the invention, the cinchona alkaloid compound used is selected from the group consisting of dihydroquinidine 1,2 dichlorophthalazine, dihydroquinidine pyridine diethyl ether, dihydroquinidine anthraquinone, dihydroquinidine 0-acetate, dihydroquinidin chlorobenzylpyrimidine dihtydroquinidine phenanthyrl, dihydroquinidine 9-0-(4'-methyl-2'-quinidyl) and other pseudoenantiomeric forms of such ligands.
DHQD-CLB, DHQD-PHN, DHQD-MEQ, DHQD-IND and other pseudoenantiomeric forms of such ligands.
The novelty in the invention lies in the preparation of multifunctional catalysts through simple exchange process for the first time and use thereof in catalytic amounts for preparing vicinal diols by tandem and/or simultaneous reactions involving Heck coupling, N-oxidation and asymmetric dihydroxylation of olefins employing oxidants in presence of cinchona alkaloid compounds. Higher yields and enantioselectivities are obtained when multifunctional catalysts are used in the synthesis of diols. Since the dihydroxylated products are important intermediates for the preparation of drugs and Pharmaceuticals, this invention that envisages reduction of toxic osmium metal content in these products is timely and appropriate. The consistent activity and enantioselectivity obtained for several cycles in multicomponent reaction makes the process economical and possible for commercial realization. Therefore, multifunctional catalysts are better option for the synthesis of vicinal diols. The use of different supports and varied compositions used in the preparation of multifunctional catalysts has no impact on its final form of catalysts with respect to activity and enantioselectivity. Thus this invention offers the best techno-economic route for the synthesis of chiral vicinal diols, intermediates for the preparation of drugs and Pharmaceuticals.
In the present invention, multifunctional catalysts have been synthesized for the first time and used in catalytic amounts for preparing vicinal diols by tandem and/or simultaneous reactions involving Heck coupling, N-oxidation and asymmetric dihydroxylation of olefins employing oxidants in presence of cinchona alkaloid compounds in a heterogeneous manner. Multifunctional catalysts are prepared by anion exchange of active species or anchoring through covalent bond formation on various supports originated from inorganic or organic. The metals immobilized on supports are responsible for the multifunctional activity of catalyst. The activity of heterogeneous multifunctional catalysts is similar or higher than the homogeneous counter parts. The higher activity is ascribed to the support effect. Higher yields and enantioselectivities are obtained with multifunctional catalysts used in the multicomponent reaction in aqueous organic solvents. Since the dihydroxylated products are important intermediateis for the preparation of drugs and Pharmaceuticals, this invention is timely and appropriate. Therefore, multifunctional catalysts are a better option for the
synthesis of vicinal diols. The multifunctional catalysts prepared irrespective of support or method of immobilization used in the preparation of multifunctional catalysts offered good yields and enantioselectivies in presence of cinchona alkaloids.
Multifunctional catalysts are prepared and used in catalytic amounts for preparing vicinal diols by muticomponent reaction using oxidants in presence of cinchona alkaloid compounds in a heterogeneous manner are described in the following examples, which are by way of illustration and should not be construed to limit the scope of the invention. Preparation of multifunctional catalysts
Example 1
Preparation of Layedred double hydroxide (LDH)-PdOs(l)
1 g of LDH was suspended in 100 ml of aqueous solution containing Na2PdCI4 and K2OsO4.2H2O (0.4 mmol each) and stirred at 25°C for 12 h under nitrogen atmosphere. The solid catalyst was filtered, washed thoroughly with 500 ml of water and vacuum dried to obtain 1.158 g of LDH-PdOs (0.34 mmol g'1 of each Pd and Os).
Example 2
Preparation of LDH-OsW (2)
1 g of LDH was suspended in 100 ml of aqueous solution containing K2OsO4.2H2O and Na2WO4.2H2O (0.4 mmol each) and stirred at 25°C for 12 h under nitrogen atmosphere. The solid catalyst was filtered, washed thoroughly with 500 ml of water and vacuum dried to obtain 1.172 g of LDH-OsW (0.34 mmol g"1 of each Os and W).
Example 3
Preparation of LDH-PdOsW (3)
1 g of LDH was suspended in 100 ml of aqueous solution containing Na2PdCI4, K2OsO4.2H2O and Na2WO4.2H2O (0.3 mmol each) and stirred at 25°C for 12 h under nitrogen atmosphere. The solid catalyst was filtered, washed thoroughly with 500 ml of water and vacuum dried to obtain 1.181 g of LDH-PdOsW (0.25 mmol g-1 of each Pd, Os and W).
Example 4
Preparation of resin -PdOsW (4)
Resin was obtained by quaternization of triethylamine (2.1 ml, 21 mmol) with 1 g of chloromethylated styrene-divinylbenzene copolymer (Merrifield resin, capacity -2.1 mequiv/g) in chloroform (20 ml) under reflux for 24 h. 1 g of quaternary ammonium resin was suspended in 100 ml of aqueous solution containing Na2PdCI4, K2Os4.2H2O and Na2WO4.2H2O (0.25 mmol each) and stirred at 25°C for 12 h under nitrogen atmosphere. The solid catalyst was filtered, washed thoroughly with 500 ml of water and vacuum dried to obtain resin-PdO2W (0.2 mmol g -1 of each Pd, Os; and W).
Example 5
Preparation of SiO2-PdOsW (5)
Modified silica was obtained by quaternisation of triethylamine (0.7 ml, 7 mmol) with bromopropylsilica (capacity 0.7 mequiv/g) in chloroform (20 ml) under reflux for 24 h. 1 g of quaternary ammonium silica was suspended in 100 ml of aqueous solution containing Na2PdCI4, K2OsO4.2H2O and Na2WO4.2H2O (0.11 mmol each) and stirred at 25°C for 12 h under nitrogen atmosphere. The solid catalyst was filtered, washed thoroughly with 500 ml of water and vacuum dried to obtain SiO2-PdOsW (0.1 mmol G-1 of each Pd, Os and W).
Example 6
Preparation of Silica gel supported (SGS)-QN2PHAL-PdOs (7)
2 g of SGS-(QN)2PHAL was treated with PdCI2 (2 mmol) in acetone (10 ml) under reflux for 24 h. The dark yellow powder was filtered, washed with acetone, then stirred with hydrazine hydrate (1.5 ml) and 10 ml) at room temperature for 4 h. The resulting solid was filtered, washed with ethanol and dried under vacuum for 1 h to give a light green colored solid, SGS-(QN)2PHAL-Pd (0.2 mmol of palladium per gram), subsequent comlexation with OsO4 (0.2 mmol per gram) obtained SGS-(QN)2PHAL-PdOs.
Example 8 Preparation of SGS-(QN)2PHAL-PdOsW (8)
SGS-(QN)2PHAL-PdOs as synthesized in example 7 was mixed with 1 equivalent of tungstate exchanged quaternary ammonium form of silica to obtain SGS-(QN)2PHAL-PdOsW. Synthesis of chiral diols
The synthesis of chiral diols was performed using the following methods in order to evaluate multifunctional catalysts s of the present invention.
Example 9 Synthesis of (R,R)-(+)-l ,2-diphenyl-l,2-ethanediol using LDH-PdOs
1 mol% of LDH-PdOs, 1 mM iodobenzene, 1 mM styrene and 1.1 mM EtsN were stirred at 70°C for 8 h. At this stage, the heating was stopped and a mixture of (DHQD)2PHAL (Imol %) and 1.3 mM NMO in 5 ml of'butanol-water (5:1) was added and stirred at room temperature. After completion of the diol formation (4-6 h, as monitored by TLC), the catalyst was filtered and washed with ethyl acetate. The combined filtrates were extracted with IN HC1 (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cw-diol.
Example 10 Synthesis of (R,R)-(+)- L,2-diphenyl-l,2-ethanediol using LDH-OsW
LDH-OsW (0.01 mmol), NMM(0.5 mmol), (DHQD)2PHAL(0.03 mmol, 23 mg) and 1/5 of the H2O2 (1/5 x 1.5 mmol) were taken in a round bottomed flask containing 'BuOH-water (3:1, 5 mL) and stirred at room temperature for 20 min. To this mixture was added an olefin (1 mmol) and the rest of the H202 over a period of 10 h using separate syringe pumps. After the addition was complete the reaction mixture was stirred for another 2 h and filtered, washed with ethyl acetate. The combined filtrates were extracted with IN HC1 (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cw-diol.
Example 11 Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using LDH-PdOsW
1 mol% of LDH-PdOsW, 1 mM iodobenzene, 1 mM styrene and 1.1 mM Et3N were stirred at 70°C for 8 h. After completion of Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD)2PHAL (1 mol%) and 0.5 mM of NMM in 5 ml of 'butanol-water (5:1) was added in one portion to the reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12 h. After the addition was complete, the resulting solution
was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate. The combined filtrates were extracted with IN HCI (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cis-diol. The recovered catalyst was reused with consistent activity for four runs (examples 28-32).
Example 12 Synthesis of (R,R)-(+)-l ,2-diphenyl-l,2-ethanediol using resin-PdOsW
1 mol% of resin-PdOsW, 1 mM iodobenzene, 1 mM styrene and 1.1 mM EtsN were stirred at 70°C for 8 h. After completion of Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD)2PHAL (1 rnol%) and 0.5 mM of NMM in 5 ml of 'butanol-water (5:1) was added in one portion to the reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12 h. After the addition was complete, the resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate. The combined filtrates were extracted with IN HCI (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to get the corresponding cis-diol.
Example 13 Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using SiO2-PdOsW
1 mol% of SiOz-PdOsW, 1 mM iodobenzene, 1 mM styrene and 1.1 mM EtsN were stirred at 70°C for 8 h. After completion of Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD)2PHAL (1 mol%) and 0.5 mM of NMM in 5 ml of 'butanol-water (5:1) was added in one portion to the reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12h. After the addition was complete, the resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate. The combined filtrates were extracted with IN HCI (2x5 mL) to recover the chiral ligand from the aqueous layer, After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cts-diol.
Example 14
Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using SGS-(QN)2PHAL-OsTi system by H2O2 oxidant.
SGS-(QN)2PHAL-OsTi (0.01 mmol), NMM(0.25 mmol), TEAA(2 mmol) and 1/5 of the H2O2 (1/5 x 1.5 mmol) were taken in a round-bottomed flask containing 'BuOH-water (3:1, 5 mL) and stirred at room temperature for 20 min. To this mixture was added an olefin (1 mmol) and the rest of the H2O2 over a period of!2h using separate syringe pumps. After
the addition was complete the reaction mixture was stirred for another 2 h and the catalyst was filtered and washed with ethyl acetate. The solvent was removed and the crude material was chromatographed on silica gel to afford the corresponding cis-diol.
Example 15
Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using SGS-(QN)2PHAL-PdOs by NMO oxidant.
Catalyst? (100 rng, 0.02 mmol), 1 mM iodobenzene, 1 mM styrene and 1.1 mM EtsN in acetonitrile (5 ml) were stirred at 70°C for 8 h. At this stage, the heating was stopped and solvent was removed under vacuum. 1.3 mM of NMO in 5 ml of 'butanol-water (3:1) was added and stirred at room temperature for 12 h. After completion of the reaction, the catalyst was filtered and washed with ethyl acetate. After removing the solvent, the crude material was chromatographed on silica gel to afford the corresponding cw-diol.
Example 16
Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using SGS-(QN)2PHAL-PdOs by K3Fe(CN)6 oxidant.
Catalyst (100 mg, 0.02 mmol),l mM iodobenzene, 1 mM styrene and 4 mM K2COs in acetonitrile (5 ml) were stirred at 70°C for 8 h. At this stage, the heating was stopped and solvent was removed under vacuum. 3 mM of K3(FeCN)6 in 10 ml of 'butanol-water (1:1) was added and stirred at room temperature for 12 h. After completion of the reaction, the catalyst was filtered arid washed with ethyl acetate. After removing the solvent, the crude material was chromatographed on silica gel to afford the corresponding cis-diol.
Example 17
Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using Na2PdCl4/K2OsO4.2H2O by NMO oxidant.
Na2PdCl4 (1 mol%), K2OsO4.2H2O (1 mol%), 1 mM iodobenzene, 1 mM styrene and 1.1 mM EtaN were stirred at 70°C for 8 h. At this stage, the heating was stopped and a mixture of (DHQD)2PHAL (Imol %) and 1.3 mM NMO in 5 ml of'butanol-water (5:1) was added and stirred at room temperature. After completion of the diol formation (4-6 h, as monitored by TLC), toluene was added to the reaction mixture to get the phase separation and the aqueous phase was, extracted with toluene ( 2x 5 mL). The organic phase was washed with IN HCI to recover the chiral ligand. The organic solvent was removed and the crude material was chromatographed on silica gel to afford the corresponding cis-diol.
Example 18 Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using K2OsO4.2H2O/Na2WO4.2H2O
K2OsO4 .2H2O (3.68 mg, 0.01 mmol), Na2WO4.2H2O (3.29 mg, 0.01 mmol), NMM(0.5 mmol), (DHQD)2PHAL(0.03 mmol, 23 mg) and 1/5 of the H2O2 (1/5 x 1.5 mmol) were taken in a round bottomed flask containing 'BuOH-water (3:1,5 mL) and stirred at room temperature for 20 min. To this mixture was added an olefin (1 mmol) and the rest of the H2O2 over a period of 10 h using separate syringe pumps. After the addition was complete the reaction mixture was stirred for another 2 h. Toluene was added to the reaction mixture to get the phase separation and the aqueous phase was extracted with toluene ( 2x 5 mL). The organic phase was washed with IN HC1 to recover the chiral ligand. The organic solvent was removed and the crude material was chromatographed on silica gel to afford the corresponding cw-diol.
Example 19
Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using Na2PdCl4/ K2OsO4.2H2O/ Na2WO4.2H20
Na2PdCl4 (2.94 mg, 0.01 mmol), K2OsO4 .2H2O (3.68 mg, 0.01 mmol), Na2W04.2H2O (3.29 mg, 0.01 mmol), 1 mM iodobenzene, 1 mM styrene and 1.1 mM Et3N were stirred at 70°C for 8 h. After completion of Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD)2PHAL (3 mol%) and 0.5 mM of NMM in 5 ml of'butanol-water (5:1) was added in one portion to the reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12h. After the addition was complete, the resulting solution was stirred for an additional 1 h. Toluene was added to the reaction mixture to get the phase separation and the aqueous phase was extracted with toluene ( 2x 5 mL). The organic phase was washed with IN HC1 to recover the chiral ligand. The organic solvent was removed and the crude material was chrbmatographed on silica gel to afford the corresponding cis-diol. The metal salts can be recovered and reused for the next reaction by evaporation of the aqueous phase. LDH-PdOsW catalyzed synthesis of chiral diols
Example 20 Synthesis of (R,R)-(+)-1,2-diphenyl-1,2-ethanediol
1 mol% of LDH-PdOsW, 1 mM bromobenzene, 1 mM styrene and 1.1 mM EtsN were stirred at 70°C for 16 h. After completion of the Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD)2PHAL (1 mol%) and 0.5 mM of NMM in 5 ml of'butanol-water (5:1) was added in one portion to the reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12 h. After the addition was complete, the resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl
acetate. The combined filtrates were extracted with IN HC1 (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cis-diol.
Example 21 Synthesis of (R,R)-(+)-1 -(4-methoxyphenyl),2-phenylethanediol
1 mol% of LDH-PdOsW, 1 mM 4-iodoanisole, 1 mM styrene and 1.1 mM EtsN were stirred at 70°C for 8 h. After completion of Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD)2PHAL (1 mol%) and 0.5 mM of NMM in 5 ml of 'butanol-water (5:1) was added in one portion to the reaction flask. 1.5 mM of HiC^ was then slowly added over a period of 12 h. After the addition was complete, the resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate. The combined filtrates were extracted with IN HC1 (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cis-diol.
Example 22 Synthesis of (R,R)-(+)-l-(4-methylphenyl),2-phenylethanediol
1 mol% of LDH-PdOsW, 1 mM 4-iodotoluene, 1 mM styrene and 1.1 mM EtaN were stirred at 70°C for 8 h. After completion of Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD)2PHAL (1 mol%) and 0.5 mM of NMM in 5 ml of 'butanol-water (5:1) was added in one portion to the reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12 h. After the addition was complete, the resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate. The combined filtrates were extracted with IN HC1 (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cis-diol.
Example 23 Synthesis of (R,R)-(+)-1 -(4-chlorophenyl),2-phenylethanediol
1 mol% of LDH-PdOsW, 1 mM 4-chloroi odobenzene, 1 mM styrene and 1.1 mM EtaN were stirred at 70°C for 8 h. After completion of Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD);jPHAL (1 mol%) and 0.5 mM of NMM in 5 ml of 'butanol-water (5:1) was added in one portion to the reaction flask. 1.5 mM of H2C-2 was then slowly added over a period of 12 h. After the addition was complete, the resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl
acetate. The combined filtrates were extracted with IN HC1 (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cw-diol.
Example 24 Synthesis of (R,R)-(+)-4,4'-Dimethyldiphenyl-l ,2-ethanediol
1 mol% of LDH-PdOsW, 1 mM 4-iodotoluene, 1 mM 4-methylstyrene and 1.1 mM Et3N were stirred at 70°C for 16 h. After completion of Heck coupling as monitored by TLC, heating was stopped and a mixture of (DHQD^PHAL (1 mol%) and 0.5 mM of NMM in 5 ml of 'butanol-water (5:1) was added in one portion to the reaction flask. 1.5 mM of HiOi was then slowly added over a period of 12h. After the addition was complete, resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate. Combined filtrates were extracted with IN HC1 (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cis-diol.
Example 25 Synthesis of (R,R)-(+)-4,4'-Dimethoxydiphenyl-l,2-ethanediol
1 mol% of LDH-PdOsW, 1 mM 4-iodoanisole, 1 mM 4-methoxystyrene and 1.1 mM EtsN were stirred at 70°C for 16 h. After completion of Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD);.PHAL (1 mol%) and 0.5 mM of NMM in 5 ml of'butanol-water (5:1) was added in one portion to reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12 h. After the addition was complete, resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate. The combined filtrates were extracted with IN HC1 (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cis-diol.
Example 26 Synthesis of (2S,3R)-(-)-Methyl-2,3-dihydroxy-3-phenylpfopionate
1 mol% of LDH-PdOsW, 1 mM iodobenzene, 1 mM methyl acrylate and 1.1 mM EtsN were stirred at 70°C for 8 h. After completion of Heck coupling as monitored by TLC, the heating was stopped and a mixture of (DHQD)zPHAL (1 mol%) and 0.5 mM of NMM in 5 ml of'butanol-water (5:1) was added in one portion to reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12 h. After the addition was complete, resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate.
The combined filtrates were extracted with IN HC1 (2x5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cw-diol.
Example 27 Synthesis of (2S,3R)-(-)-Ethyl-2,3-dihydroxy-3-(4-methoxyphenyl)propionate
1 mol% of LDH-PdOsW, 1 mM iodoanisole, ImM ethyl acrylate and 1.1 mM Et3N were stirred at 70°C for 8h. After completion of Heck coupling as monitored by TLC, heating was stopped and a mixture of (DHQD)2PHAL (1 mol%) and 0.5 mM of NMM in 5 ml of 'butanol-water (5:1) was added in one portion to reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12 h. After the addition was complete, resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate. The combined filtrates were extracted with IN HC1 (2 x 5 mL) to recover the chiral ligand from the aqueous layer. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cis-diol.
Example 28 Synthesis of (R,R)-(+)- l,2-diphenyl-l,2-ethanediol using SGS-(QN)2PHAL-PdOsW
1 mol% of SGS-(QN)2PHAL-PdOsW, 1 mM iodobenzene, 1 mM styrene and 1.1 mM EtaN in acetonitrile (5 ml) were stirred at 70°C for 8 h. At this stage, heating was stopped and solvent was removed under vacuum. To this 0.5 mM of NMM in 5 ml of'butanol-water (5:1) was added in one portion to reaction flask. 1.5 mM of H2O2 was then slowly added over a period of 12h. After the addition was complete, resulting solution was stirred for an additional 1 h and the catalyst was filtered and washed with ethyl acetate. After removing the solvent, the crude material was chromatographed on silica gel using hexane/ethyl acetate as an eluant to afford the corresponding cis-diol. Reuse of LDH-PdOsW in the synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol
Example 29
Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanedio! using LDH-PdOsW, which is recovered from Example 10. The reaction was performed using an identical process as in example 5 (yield 84%, ee 99%).
Example 30
Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using LDH-PdOsW, which is recovered from Example 29.
The reaction was performed using an identical process as in example 10 (yield 86%, ee 99%).
Example 31
Synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol using LDH-PdOsW, which is recovered
from Example 30.
The reaction was performed using an identical process as in example 10 (yield 84%, ee 99%).
Example 32
Synthesis of (R,R)-(+)-1.2-diphenyl-l,2-ethanediol using LDH-PdOsW, which is recovered from Example 31.
The reaction was performed using an identical process as in example 10 (yield 85%, ee 99%). The experimental results in the Examples 9 to 32 are provided in Tables 1-3. Table 1: Synthesis of (R,R)-(+)-l,2-diphenyI-l,2-ethanediol with various multifunctional catalysts.

(Table Removed)
a Yield percent after the separation by using column chromatography.
b % e.e.(e.e. means enantiomeic excess) was determined by chiral HPLC analysis
Table 3. Reuse of LDH-PdOsW in the synthesis of (R,R)-(+)-l,2-diphenyl-l,2-ethanediol

(Table Removed)
The main advantages of the present invention are:
1. The process for the synthesis of chiral diols from aryl halides and olefins in a single pot is
novel and ecofriendly. The present process dispenses with the use of soluble, toxic
osmium tetraoxide or potassium osmate dihydrate and instead uses novel heterogeneous
reusable multifunctional catalysts. The catalyst of the invention is important since it can
catalyse three different reactions by generating the precursors, pro chiral olefins and
NMO for AD reaction in situ from the readily available cheaper starting materials such as
styrenes and aryl halides thereby saving energy and time vital for a better and economical
process. The catalysts used are economical and do not present a problem of disposal.
2. Multifunctional recyclable catalysts are used as heterogeneous catalysts for synthesis of
chiral diols, thereby precluding the presence of osmium in traces with product
3. The enantioselectivity and the yields are good and the work-up procedure is simple.

We claim :
1. A process for the preparation of a chiral vicinal diol from aryl halide and
olefin using a reusable multifunctional catalyst having formula S-M,
wherein S is a support selected from the group consisting of layered
double hydroxide, resin, silica, clay, alumina and S'-NR3X wherein S' is a
unmodified support selected from resing and silica, R is an alkyl group
selected from the group consisting of methyl, ethyl, propyl and butyl, X is
selected from the group consisting of Cl, Br, I, F, OH and OAc; M is an
active metal species comprising two different transition metals essentially
one is palladium and another one is selected from the group consisting of
ruthenium, osmium, tungsten, titanium, vanadium, chromium, manganese,
iron, cobalt, nickel, copper and molybdenum, said process comprising
reacting aryl halide and olefin using the said catalyst by Heck coupling and
asymmetric dihydroxylation in the presence of an oxidant and a cinchona
alkaloid compound in a solvent selected from the group consisting of
water, acetone, acetonitrile and t-butanol, at a temperature in the range of
-20 to 200°C for a period ranging from 0.5 to 48 hours and obtaining the
desired chiral vicinal diol.
2. A process as claimed in claim 1 wherein the quantity of multifunctional
catalyst used in the reaction is in the range of 0.01 to 10 mol% of active
species with respect to the substrate.
3. A process as claimed in claims 1-2, wherein the multifunctional catalyst
used is recovered by filtration and is reused for several cycles with
consistent activity.
4. A process as claimed in claims 1-3, wherein the oxidant used is selected
from the group consisting of N-methyl morpholine N-oxide (NMO),
trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide,
potassium ferricyanide, sodium periodate and molecular oxygen.
5. A process as claimed in claims 1-4 wherein the cinchona alkaloid
compound used is selected from the group consisting of dihydroquinidine
1,2 dichlorophthalazine, dihydroquinidine pyridine diethyl ether,
dihydroquinidine anthraquinone, dihydroquinidine 0-acetate,
dihydroquinidin chlorobenzylpyrimidine dihtydroquinidine phenanthyrl,
dihydroquinidine 9-0-(4'-methyl-2'-quinidyl) and other pseudoenantiomeric
forms of such ligands.
6. A process for the preparation of a chiral vicinal diol from aryl halide and
olefin using a reusable multifunctional catalyst substantially as herein
described with reference to the exaples.